current research

Vashishtha et al. 2022

Current research

Our group has currently established the importance of the L-asparaginase in pathogenic organisms like Mycobacterium tuberculosis and Neisseria gonorrhoeae. In case of Neisseria gonorrhoeae the L-asparaginase remained highly conserved in over 15000 genomic sequences over the evolutionary course. Thus, establishing it's highly conserved nature. This helped us in formulating and screening highly efficient drugs that can be used against the increasing antibiotic resistant strains of this pathogen. Our group successfully showed the effective potential of screened drugs in ceasing the growth of Mycobacterium tuberculosis and Neisseria gonorrhoeae.

Currently we are working on misfolding, and aggregation kinetics of neurodegenerative disease associated proteins. Human Optineurin (OPTN) is one of the target proteins with implications in Primary Open Angle Glaucoma (POAG) and its mutants have been implicated in neurodegenerative diseases like the Amyotrophic Lateral Sclerosis (ALS). We are investigating the complexity of OPTN, its structural and functional characteristics through biophysical and biochemical techniques. We have shown reversibility of OPTN from unfolded states, and its chaperoning activity through prevention of thermal aggregation of other proteins. We hypothesized that disease-associated mutants of OPTN impair cellular autophagy, leading to neurodegeneration. We are now focusing on how ALS and glaucoma related OPTN mutants might affect the integrity of the proteome. While on the one hand we are working on its folding behavior, on the other hand we are deciphering the aggregation propensity of OPTN and its disease mutants.

The Current area in which our lab is actively engaged is towards discovering potential therapeutic targets of multidrug resistance bacteria. We are currently focusing on Salmonella typhi, where we identified a potential therapeutic target, cell division activator protein (CedA), which is mostly conserved. Previously we identified the functional interactome of E. coli CedA and proposed that in E. coli cells, chromosomal over-replication triggered CedA to initiate transcription of cell division regulatory elements. Currently, we are investigating the transcriptional and translational effects of Salmonella CedA on human macrophages in order to understand its pathogenesis.

Recently we have started working on viral and bacterial proteins to elucidate their role in neurodegeneration. Sequence conservation among various viral, bacterial and mammalian proteins led us to hypothesize that there is an intimate crosstalk between these proteins where they influence each other in aggregation/amyloid formation/fibrilization. By using in silico, in vitro and in cell experiments we are trying to identify proteins of viral or bacterial origins that could ‘seed’ or promote formation of toxic protein aggregates of the host proteins and trigger neurodegenerative diseases.